摘要
背景:NRG1基因的分子病变最近被描述为肺部浸润性粘液腺癌的新分子特征。 NRG1嵌合配体导致通过PI3KAKT和MAPK细胞级联的ErbB2 / ErbB3信号的异常活化。本综述旨在强调目前有关ErbB网络的知识以及NRG1放松管制对肺癌的影响,以及通过目前的药物策略将其合并到ErbB / PI3K-AKT轴调节中的作用。 方法:我们对同行评议的文献进行了书目数据库的结构化搜索,以概述关于ErbB信号放松和NRG1功能在肺癌领域的现状。检索的文件的质量使用标准的工具进行评估,135个评估包括在审查。在许多论文中,更新了影响肺癌中的ErbB受体的分子病变,但也更新了其他类型的实体瘤中的分子病变。还介绍了描述NRG1在细胞中的生理作用的文章,以供审查制备,以及报道肺癌中NRG1融合蛋白及其在异常ErbB途径活化中的意义。 结果与结论:总体而言,本综述高度评价了ErbB途径失调的新分子机制知识如何有助于获得肺癌患者分子状态的新见解,揭示患者分层的新分子标记。此外,这最终导致选择旨在抑制Nrg1-ErbB3之间的结合的新化合物作为阻断ErbB细胞内信号传导的良好替代方式。
关键词: ErbB网络,ErbB3,NRG1融合,肺癌,靶向治疗,对治疗的抵抗
Current Medicinal Chemistry
Title:NRG1-ErbB Lost in Translation: A New Paradigm for Lung Cancer?
Volume: 24 Issue: 38
关键词: ErbB网络,ErbB3,NRG1融合,肺癌,靶向治疗,对治疗的抵抗
摘要: Background: Molecular lesions of the NRG1 gene were recently described as a new molecular feature of Invasive Mucinous Adenocarcinoma of the lung. The NRG1 chimeric ligand leads to aberrant activation of the ErbB2/ErbB3 signaling via PI3K–AKT and MAPK cellular cascades. This review aims to highlight the current knowledge about the ErbB network and the effect of NRG1 deregulation in lung cancer and their merger into the ErbB/PI3K-AKT axis modulation by current pharmacologic strategies.
Methods: We performed a structured search of bibliographic databases for peer-reviewed literature to outline the state of the art with regard ErbB signaling deregulation and NRG1 function in lung cancer. The quality of retrieved papers was assessed using standard tools and one hundred thirty-five were included in the review. In many papers the molecular lesions affecting the ErbB receptors in lung cancer but also in other type of solid tumors were updated. Papers describing the physiological role of NRG1 in cells was also screened for the review preparation, as well as the paper reporting NRG1 fusions in lung cancer and their implication in aberrant ErbB pathway activation.
Results and Conclusion: Overall, this review highpoints how the knowledge of new molecular mechanisms of ErbB pathway deregulation may help in gaining new insights into the molecular status of lung cancer patients and unveil a novel molecular markers of patients' stratification. Moreover, this ultimately led the selection of new compounds designed to inhibit the bound between Nrg1-ErbB3 as a good alternative way to block the ErbB intracellular signaling.
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Cite this article as:
NRG1-ErbB Lost in Translation: A New Paradigm for Lung Cancer?, Current Medicinal Chemistry 2017; 24 (38) . https://dx.doi.org/10.2174/0929867324666170911170554
DOI https://dx.doi.org/10.2174/0929867324666170911170554 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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